This research project was designed to gain some insight into the pathogenesis of glomerulonephritis and proteinuria in murine lupus. Immunopathologic, immunochemical and biological characteristics of immunoreactants are investigated in sera, tissue, and tissue-eluate of untreated and drug-treated (corticosteroid, cyclophosphamide, azathioprine) NZB/W mice. Glomerular permeability properties are assessed by ultrastructural tracing of endogenous and exogenous protein filtration across the capillary wall, by biochemical and histochemical quantitation of sialic acid residues in glomeruli, and by characterization and quantitation of urinary proteins. The specific objectives are: a) to study characteristics of deposited immune complexes such as immunoglobulin composition, antiDNA activity, interaction of antiDNA antibody with structural components of various tissues, and ability to bind and to activate complement in vitro, b) to quantitate antiDNA antibody and complement in sera and eluates of various tissues, c) to characterize functional properties of complement activation, d) to characterize the distribution and composition of immune complexes in tissues, e) to assess the extent of tissue injury and renal function compromise, f) to study the glomerular permeability properties during the development of and after well established renal disease, and g) to correlate immunopathologic and/or glomerular permeability properties with quantity (antiDNA antibody) and location of immune complexes, immunochemical and biological characteristics of tissue-eluted antiDNA antibody, and pattern of activation in serum and quantity of complement in tissues in treated and untreated animals. A better understanding of the pathogenesis of glomerulonephritis and proteinuria in this animal model is of relevance to human lupus nephritis and, in a broad sense, to a variety of related immunologic disorders in man.